Atovaquone-proguanil

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Atovaquone-proguanil, made by Smith Kline Glaxo and approved by the U.S. Food and Drug Administration in 2000, is a fixed-combination antimalarial drug for chemoprophylaxis and treatment. It is labeled for treatment and prevention of Plasmodium falciparum, especially chloroquine-resistant. Off-label uses include prevention of Plasmodium vivax and treatment of babesiosis.

Mechanism of action

The two components block with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a tetrahydrofolate dehydrogenase inhibitor]]. Inhibition of tetrahydrofolate dehydrogenase in Plasmodium sp. disrupts deoxythymidylate synthesis.[1]

Drug-drug interactions

There are adverse interactions with tetracycline, metoclopramide and rifampin.

References